Novel antioxidant peptides from jellyfish (Nemopilema nomurai) hydrolysate: identification, activity, and potential...

To explore the antioxidant function and application potential of bioactive peptides derived from jellyfish, this study focused on the identification, activity, and potential mechanisms of novel antioxidant peptides from JP-FC, a peptide fraction prepared via enzymatic hydrolysis of jellyfish Nemopilema nomurai. JP-FC exhibited potent antioxidant capacity, with EC₅₀ of 1.03, 2.05, and 4.94 mg/mL against hydroxyl radicals (·OH), superoxide anion radicals (O₂^-·), and 1,1-diphenyl-2-picrylhydrazyl radicals (DPPH·), respectively. LC-MS/MS combined with bioinformatic analysis identified three key peptides, FNPPPP, PPPMQPPP, and WDAPLLG, which exhibited EC₅₀ values of 0.86, 1.25, and 1.69 mg/mL, respectively, in hydroxyl radical scavenging assays. In a H₂O₂-induced oxidative stress model in immortalized human keratinocytes (HaCaT cells), FNPPPP, and PPPMQPPP significantly decreased intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels while enhancing superoxide dismutase (SOD) activity, demonstrating strong antioxidant and cytoprotective effects. Molecular docking suggested potential interactions between these peptides and Kelch-like ECH-associated protein 1 (Keap1), implying a possible association with nuclear factor erythroid 2-related factor 2 (Nrf2)-related antioxidant regulation that warrants further experimental validation. The RT-qPCR analysis showed that peptide treatment modulated the transcriptional expression of Keap1 and downstream antioxidant-response genes (HO-1 and NQO1) under oxidative stress conditions. Overall, the novel antioxidant peptides in JP-FC indicate that JP-FC is a promising natural antioxidant source, providing a scientific foundation for the development of jellyfish-derived peptides in functional food, cosmetic and pharmaceuticals. Moreover, this study supports the high-value utilization of jellyfish biomass by highlighting its dual dietary and health-promoting potential as a traditional food resource with nutraceutical relevance. Further work is required to enhance peptide stability and verify antioxidant mechanisms under physiologically relevant conditions.